Japanese Unexamined Patent Publication No.119593/1973 discloses a process for preparing a 3-substituted cephem compound by coupling a carbonyl compound with a 3-phosphoranilideneethyl cephalosporin compound derived from a 3-halogenomethyl cephalosporin compound.
Japanese Unexamined Patent Publication No.37788/1986 and. Helv. Chim. Acta, 57, 2024 (1974) disclose processes for preparing a 3-substituted arylmethyl cephem compound by coupling a 3-acetoxymethyl cephalosporin compound with a substituted benzene in the presence of a Lewis acid.
A typical process for preparing the 3-substituted cephem compound was reported which comprises subjecting to coupling reaction a 3-trifluorooxycephem (A) or a 3-chloromethylcephem (B) and an organotin compound in the presence of a palladium catalyst as illustrated below in a reaction scheme (J. Org. Chem., 55, 5833-5847, 1990): ##STR1##
However, the foregoing known processes all require an expensive starting material having a cephalosporin skeleton. The process shown above in the reaction scheme has the drawback, from a commercial viewpoint, of using a theoretical amount of a detrimental organotin compound and an expensive palladium catalyst.
On the other hand, attempts have been made to prepare a 3-substituted cephem compound from an inexpensive penicillin derivative. For example, a process is known which comprises reacting an allenyl-.beta.-lactam compound represented by the formula ##STR2## wherein R.sup.1 is a hydrogen atom, a halogen atom, an amino group or a protected amine group, R.sup.2 is a hydrogen atom, a halogen atom, a lower alkoxy group, a lower acyl group, a lower alkyl group, a lower alkyl group having a hydroxyl group or a protected hydroxyl group as a substituent, a hydroxyl group or a protected hydroxyl group, R.sup.3 is a hydrogen atom, or a carboxylic acid-protecting group, R.sup.4 is an aryl group optionally having a substituent or a nitrogen-containing aromatic heterocyclic group optionally having a substituent, and m is 0 or 2, namely the starting material used in the process of the invention, with a nucleophile represented by the formula wherein Y is a nucleophile residue, giving a 3-substituted cephem compound represented by the formula ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 and Y are as defined above (Japanese Unexamined Patent Publication No.282387/1992). This process, however, can not produce the contemplated compound of the present invention because the compound of the formula (D) wherein Y is an alkenylmethyl group or arylmethyl group can not act as a nucleophile. The aforesaid publication teaches nothing about some features of the present invention such as the use of a specific metallic reducing agent and a specific organohalogen compound.
A technique for preparing a compound having a .beta.-lactam ring is disclosed, for example, in Japanese Unexamined Patent Publication No.211055/1992, the technique using lead, copper, titanium, bismuth, antimony or the like as a metallic reducing agent along with a metal such as aluminum, zinc, magnesium, tin or the like which have a higher ionization tendency than said metallic reducing agent. Stated more specifically, the publication discloses a process comprising reacting a halogenated .beta.-lactam compound represented by the formula ##STR4## wherein R.sup.a is an amino group or a protected amino group, R.sup.b is a hydrogen atom or a carboxyl-protecting group, R.sup.c is a hydrogen atom or a hydroxyl-protecting group, and Ar is an aryl group optionally having a substituent with said metallic reducing agent and a metal having a higher ionization tendency than said metallic reducing agent, giving a 3-hydroxycephem derivative represented by the formula ##STR5## wherein R.sup.a, R.sup.b and R.sup.c are as defined above. The starting compound of the formula (F) used in the process is different from the starting compound used in the present invention although they have the same lactam skeleton, because the nitrogen atom of said skeleton is substituted at different positions between the two compounds. Further, the publication does not set forth the use of a specific organohalogen compound at all.
Moreover, when the allenyl-.beta.-lactam compound represented by the formula (1) is reacted with the metallic reducing agent taught in Japanese Unexamined Patent Publication No.211055/1992, merely a 2-exo-methylene penam derivative can be produced (Japanese Unexamined Patent Publication No.97864/1993), that is to say, the 3-substituted cephem derivative contemplated in the present invention can not be obtained.